Figure 5

Splice insert in SS#4 causes a molecular switch. Splice insert-free βLNS-SS#4 (PDB ID: 3B3Q; left panel) can bind efficiently to neuroligin (Nlgn) and leucine-rich repeat proteins (LRRTM), which have overlapping binding epitopes. The prolonged conformation caused by an insert in SS#4 (orange/red; from PDB ID: 2R1B) blocks binding to Nlgn and LRRTM, and instead allows the binding of cerebellin (Cbln, middle panel). This structure of βLNS + SS#4 is in equilibrium with an additional conformation (PDB ID: 3 MW2), in which β10 (cyan) is replaced by part of the SS#4 insert (orange, right panel). In the latter, Nlgn and LRRTM binding is restored, while interaction with Cbln should be abolished. The diagrams were made using the actual structural coordinates and PyMOL software (Schrödinger, Mannheim, Germany).